Anticipation of epileptic seizures from standard EEG recordings.
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Biomedical subjects
Publications and source records attributed to S Van Huffel.
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We studied glycogen synthesis from glucose in perfused livers of fed (n = 4) and 24 h starved (n = 7) rats. Glycogenolysis was inhibited by BAY R3401 (150 microM) and proglycosyn (100 microM). After 60 min, we replaced 99% (13)C-1 glucose by natural abundance glucose. This pulse-chase design allowed us to recognize residual ongoing futile glycogen turnover from the release of initially deposited (13)C-label, into the (13)C-free chase medium. Net residual turnover was less than 2 +/- 0.7% and 0.6 +/- 0.2% of 1-(13)C glycogen deposition rates of 0.31 +/- 0.04 and 0.99 +/- 0.04 micromol glucose g(-1) min(-1), in starved and fed livers, respectively. The 1-(13)C glycogen signal was monitored throughout the experiment with proton-decoupled (13)C NMR spectroscopy and analyzed in the time domain using AMARES. We noticed progressive line-broadening in any single experiment in the chase phase. One or a sum of two to three overlapping Lorentzians, with different exponential damping factors, were fitted to the signal. When the S/N was better than 40, the fit always delivered a small and a broad component. In the chase phase, the fit with a single Lorentzian resulted in a decline of glycogen signal by about 15 +/- 4 and 12 +/- 2% in starved and fed rats, respectively. This apparent decline in 1-(13)C glycogen signal could not be accounted for by the appearance of equivalent amounts of (13)C-labeled metabolites in the perfusate. The fit with a sum of two Lorentzians resulted in a decline of glycogen signal intensity of 7 +/- 5 and 5 +/- 3% in starved and fed rats, respectively, which reduced the apparent turnover to 8 +/- 9% and 6 +/- 4%, respectively. Quantification of the growing (13)C-1 glycogen signal requires a model function that accommodates changes in line shape throughout the period under study.
In this work, we develop and evaluate several least squares support vector machine (LS-SVM) classifiers within the Bayesian evidence framework, in order to preoperatively predict malignancy of ovarian tumors. The analysis includes exploratory data analysis, optimal input variable selection, parameter estimation, and performance evaluation via receiver operating characteristic (ROC) curve analysis. LS-SVM models with linear and radial basis function (RBF) kernels, and logistic regression models have been built on 265 training data, and tested on 160 newly collected patient data. The LS-SVM model with nonlinear RBF kernel achieves the best performance, on the test set with the area under the ROC curve (AUC), sensitivity and specificity equal to 0.92, 81.5% and 84.0%, respectively. The best averaged performance over 30 runs of randomized cross-validation is also obtained by an LS-SVM RBF model, with AUC, sensitivity and specificity equal to 0.94, 90.0% and 80.6%, respectively. These results show that the LS-SVM models have the potential to obtain a reliable preoperative distinction between benign and malignant ovarian tumors, and to assist the clinicians for making a correct diagnosis.
Magnetic resonance spectroscopy (MRS) has been shown to be a potentially important medical diagnostic tool. The success of MRS depends on the quantitative data analysis, i.e., the interpretation of the signal in terms of relevant physical parameters, such as frequencies, decay constants, and amplitudes. A variety of time-domain algorithms to extract parameters have been developed. On the one hand, there are so-called blackbox methods. Minimal user interaction and limited incorporation of prior knowledge are inherent to this type of method. On the other hand, interactive methods exist that are iterative, require user involvement, and allow inclusion of prior knowledge. We focus on blackbox methods. The computationally most intensive part of these blackbox methods is the computation of the singular value decomposition (SVD) of a Hankel matrix. Our goal is to reduce the needed computational time without affecting the accuracy of the parameters of interest. To this end, algorithms based on the Lanczos method are suitable because the main computation at each step, a matrix-vector product, can be efficiently performed by means of the fast Fourier transform exploiting the structure of the involved matrix. We compare the performance in terms of accuracy and efficiency of four algorithms: the classical SVD algorithm based on the QR decomposition, the Lanczos algorithm, the Lanczos algorithm with partial reorthogonalization, and the implicitly restarted Lanczos algorithm. Extensive simulation studies show that the latter two algorithms perform best.
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Several studies support the idea that the use of pacifiers can reduce the risk of Sudden Infant Death Syndrome. To investigate the effect of non-nutritive sucking (NNS), we measured heart rate, abdominal respiration, EMG and arterial oxygen saturation of 20 neonates. Also, in 10 of these neonates, changes in cerebral hemoglobin concentrations were acquired by means of near-infrared spectroscopy. Using a parametric technique to model the heart rate as a sum of exponentially damped sinusoids, two main frequency components were found in the heart rate during NNS: a frequency of approximately 0.08 Hz due to the alternation of sucking bursts and pauses, and a frequency of approximately 0.8 Hz that reflects the influence of the respiration. Our analysis shows that it is the alternation of bursts and pauses itself that causes the increased heart rate variability, and that this is not due to increased effort. This suggests that the neuronal mechanism regulating NNS also stimulates the heart rate. From our measurements, no effect of NNS on cerebral or peripheral oxygenation could be found. Furthermore, we show that our model-based signal processing technique is well suited for the analysis of non-stationary biomedical signals.
OBJECTIVE: To evaluate the ultrasound features of the endometrium and ovaries in women on etonogestrel implant, and to correlate these features with the bleeding pattern. METHODS: Observational study including 188 consecutive women presenting for follow-up transvaginal ultrasound examination after insertion of an etonogestrel implant contraceptive device. Thirty women had more than one follow-up examination. The bleeding pattern was considered abnormal if, in the last 3 months, there were more than five episodes of vaginal bleeding, or there was prolonged bleeding exceeding 14 consecutive days. RESULTS: At first follow-up examination, the mean age was 29.7 years and 47% of women had an abnormal bleeding pattern. Most bleeding episodes were of less intensity than menses. The mean endometrial thickness (ET) on ultrasound was 2.9 mm (standard deviation, 2.0). Ovarian follicle growth exceeding 5 mm was observed in 60% of the cases. Ovulation was demonstrated in one woman. Univariate analysis showed a positive association (P < 0.01) between ET, bleeding pattern, and bleeding intensity. Follicle growth was positively associated (P < 0.01) with ET, bleeding pattern, and interval between insertion and examination. Multivariate analysis showed that the ET was on average 1.25 mm greater in women with abnormal bleeding (P = 0.0001). The odds of finding follicle growth were 2.8 times higher (95% confidence interval, 1.2-6.2) in women presenting with a three-layer type of endometrial morphology. There was no association between the other patients' characteristics and the bleeding pattern. CONCLUSIONS: Abnormal uterine bleeding in women on etonogestrel implant was associated with follicle growth and a thicker, three-layer type of endometrium, suggesting incomplete ovarian inhibition and estrogen stimulation of the endometrium.
OBJECTIVES: To evaluate the color Doppler and gray-scale sonographic appearance of the uterus after pregnancy, with special attention to the occurrence of areas of enhanced vascularity and placental remnants. PATIENTS AND METHODS: Cross-sectional observational study involving 385 consecutive women presenting at their first visit after pregnancy. The uterus was evaluated using ultrasound with color Doppler. In the presence of placental remnants, blood was sampled for measurement of beta human chorionic gonadotropin (beta hCG), hemoglobin (Hb) and infectious parameters. If indicated, a dilatation and curettage was performed. RESULTS: In 8.3% of women, areas of enhanced vascularity were detected with color Doppler examination. Most cases (68.9%) were focal areas of one or more vessels. In 2.6% of patients abnormal vascularity extended over a large area of the whole myometrium. In 6.75% of cases, placental remnants were detected. In 46% of these, blood sampling revealed beta hCG levels below 30 mIU/mL; serological infection parameters and Hb concentration were within the normal range. CONCLUSIONS: Areas of enhanced vascularity of the uterus, ranging from a focal vascular pedicle to a larger area of the myometrium, are relatively common after pregnancy. They are predominantly seen in the presence of placental remnants, in the early postpartum period and after instrumental or manual delivery of the placenta. There are no clear risk factors for retained placental tissue, besides the history of blood transfusion in the early postpartum, and perhaps multigravidity. Serology is of little help in the diagnosis of retained gestational products. The knowledge of the ultrasound and color Doppler features of the uterus after pregnancy may prove of practical value for the management of abnormal uterine bleeding in the postpartum period.
AIM: To describe normal values of the cerebral tissue oxygenation index (TOI) in premature infants. METHODS: TOI was measured by spatially resolved spectroscopy in preterm infants on the first 3 days of life. Infants with an abnormal cranial ultrasound were excluded. Other simultaneously measured variables were PaO(2), PaCO(2), pH, mean arterial blood pressure, heart rate, haemoglobin, glycaemia, and peripheral oxygen saturation. RESULTS: Fifteen patients with a median postmenstrual age of 28 weeks were measured. There was a significant increase in median TOI over the first 3 days of life: 57% on day 1, 66.1% on day 2, and 76.1% on day 3. Multiple regression analysis showed no correlation between TOI and postmenstrual age, peripheral oxygen saturation, mean arterial blood pressure, PaO(2), PaCO(2), and haemoglobin concentration. CONCLUSION: Cerebral TOI increases significantly in the first 3 days of life in premature babies. This increase probably reflects the increase in cerebral blood flow at this time.
The nuclear factor kappaB (NF-kappaB) plays a central role in the regulation of genes implicated in immune responses, inflammatory processes, and apoptotic cell death. The zinc finger protein A20 is a cellular inhibitor of NF-kappaB activation by various stimuli and plays a critical role in terminating NF-kappaB responses. The underlying mechanism for NF-kappaB inhibition by A20 is still unknown. A20 has been shown to interact with several proteins including tumor necrosis factor (TNF) receptor-associated factors 2 and 6, as well as the inhibitory protein of kappaB kinase (IKK) gamma protein. Here we report the cloning and characterization of ABIN-2, a previously unknown protein that binds to the COOH-terminal zinc finger domain of A20. NF-kappaB activation induced by TNF and interleukin-1 is inhibited by overexpression of ABIN-2. The latter also inhibits NF-kappaB activation induced by overexpression of receptor-interacting protein or TNF receptor-associated factor 2. In contrast, NF-kappaB activation by overexpression of IKKbeta or direct activators of the IKK complex, such as Tax, cannot be inhibited by ABIN-2. These results indicate that ABIN-2 interferes with NF-kappaB activation upstream of the IKK complex and that it might contribute to the NF-kappaB-inhibitory function of A20.
The tumor necrosis factor (TNF) inducible protein A20 is a potent inhibitor of nuclear factor-kappaB (IkappaB)-mediated gene expression in response to TNF and several other stimuli. The C-terminal domain of A20 is characterized by seven zinc finger structures. Here, we show that a minimum of four zinc fingers is required to inhibit TNF-induced nuclear factor-kappaB (NF-kappaB) activation to a level that is comparable to that obtained with the wild-type A20 protein. However, there was no strict requirement for a particular zinc finger structure, since a mutant A20 protein containing only the first four zinc fingers was as potent as a mutant protein containing only the last four zinc fingers. A similar functional redundancy of the A20 zinc fingers was also observed for binding of A20 to a number of other proteins, including two novel NF-kappaB inhibitory proteins (ABIN-1, ABIN-2), A20 itself, the anti-apoptotic protein TXBP151, and a regulatory component of the IkappaB kinase complex, IKKgamma. Moreover, we demonstrate that complete loss of binding of any of these proteins correlates with complete loss of A20's ability to inhibit TNF-induced NF-kappaB activation. However, binding of IKKgamma as such is not sufficient for inhibition of NF-kappaB dependent gene expression in response to TNF.
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Suppressing the solvent peak is important in many applications of biomedical NMR spectroscopy in order to quantify the metabolites with a great accuracy. Among the postprocessing methods proposed in the literature, many deal with the concept of filtering. However, several proposals lack a theoretical perspective and some have not been explicitly applied to quantification problems. The present article is intended to bridge this gap: five methods are analyzed from a theoretical perspective. Subsequently the different methods are applied to the same set of data, and then the latter are quantified using the model fitting method AMARES. With our set, the scheme proposed by T. Sundin et al. (J. Magn. Reson. 139(2), 189-204 (1999)) proved to be the most reliable method.
The recording of somatosensory evoked potentials (SEPs) is a non-invasive routine clinical testing procedure in neurology. For trigeminal nerve stimulation, however, SEPs have not received a widespread clinical attention. A variety of protocols and procedures have been used to record trigeminal SEPs (TSEPs). Differences encountered include the stimulation mode, site and frequency, the recording electrode position and data acquisition parameters. This has resulted in a diversity of recorded TSEP signals, making comparisons almost impossible. The general picture shows a number of short latency waves (within 3 ms) of peripheral origin, followed by at least two longer latency waves (12-15 ms and 19-22 ms). Furthermore, potential waves with a very long latency (> 100 ms) follow when the response is produced by painful stimulation. The origin of the long and very long latency waves is still a matter of debate. In order to allow reliable data interpretation and comparisons between the outcome of different studies, a standardized protocol should be applied for TSEP recordings. By providing an overview, this paper aims to mark a step forward in the harmonization of TSEP protocols with respect to the neural processes of interest. Further studies should also encounter the potential application of other neuroimaging techniques, such as functional magnetic resonance imaging or positron emission tomography, preferably in combination with TSEP recordings.
Proper gene expression and cell growth are critical for the survival of all organisms. Nuclear factor-kappa B (NF-kappa B)-dependent gene expression and apoptosis play crucial roles in numerous cellular processes, and defects in their regulation may contribute to a variety of diseases including inflammation and cancer. Although there has recently been tremendous progress in our understanding of the signaling pathways that lead to NF-kappa B activation and apoptosis, signaling mechanisms that negatively regulate these processes are only partially understood. This review deals with the zinc finger protein A20, which has been characterized as a dual inhibitor of NF-kappa B activation and apoptosis. Its inducible expression by a wide variety of stimuli, including cytokines such as tumor necrosis factor, interleukin-1, and CD40, as well as bacterial and viral products such as lipopolysaccharide, Epstein-Barr virus latent membrane protein 1, and human T-cell leukemia virus type I Tax, suggests that it is involved in the negative feedback regulation of signaling. We will discuss the possible underlying mechanisms, placing emphasis on the role of several A20-binding proteins that have recently been described. Moreover, evidence is presented that A20 and A20-binding proteins are potential novel therapeutic tools in the treatment of a variety of diseases.
In this paper the possibility of obtaining accurate estimates of parameters of selected peaks in the presence of unknown or uninteresting spectral features in biomedical magnetic resonance spectroscopy (MRS) signals is investigated. This problem is denoted by frequency-selective parameter estimation. A new time-domain technique based on maximum-phase finite impulse response (FIR) filters is presented. The proposed method is compared to a number of existing approaches: the application of a weighting function in the time domain, frequency domain fitting using a polynomial baseline, and the time-domain HSVD filter method. The ease of use and low computational complexity of the FIR filter method make it an attractive approach for frequency-selective parameter estimation. The methods are validated using simulations of relevant (13)C and (31)P MRS examples.
Very weak and noisy trigeminal somatosensory evoked potentials (TSEPs) are considered, which are successfully evoked by electrical stimulation of the trigeminal nerve of 15 patients with endosseous oral implants. As TSEP analysis provides an objective means of assessing neuronal function, it is considered to be a promising tool for investigating tactile sensation through anchoring implants in bone. For this purpose, a study of TSEP signals acquired from patients with endosseous oral implants has been carried out. Since TSEPs are severely contaminated by background ongoing electrical activities of the brain, a methodology is developed for statistically detecting the transient signal (TSEP) in the biological noise (EEG). For nine out of 15 patients, transient signals are detected in the background EEG activity. The TSEPs of these nine patients are subjected to further analysis. A multichannel singular value decomposition (SVD)-based filtering method is applied which successfully separates out the most energetic TSEPs from the background EEG, thereby increasing significantly the SNR of the recorded signals and improving extraction of the characteristic components of the TSEPs. It is shown that the most prominent feature of the TSEP signals for patients with endosseous oral implants is a wave with peak latency between 9 and 15 ms, generally followed by a wave between 25 and 28 ms or 34 and 38 ms for the specific cortical response areas.